Department of Urology and Key Laboratory of Systems Biomedicine (Ministry of Education), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
Prostate. 2020 May;80(6):508-517. doi: 10.1002/pros.23965. Epub 2020 Mar 2.
As a rare subtype of prostate carcinoma, basal cell carcinoma (BCC) has not been studied extensively and thus lacks systematic molecular characterization.
Here, we applied single-cell genomic amplification and RNA-Seq to a specimen of human prostate BCC (CK34βE12 /P63 /PAP /PSA ). The mutational landscape was obtained via whole exome sequencing of the amplification mixture of 49 single cells, and the transcriptomes of 69 single cells were also obtained.
The five putative driver genes mutated in BCC are CASC5, NUTM1, PTPRC, KMT2C, and TBX3, and the top three nucleotide substitutions are C>T, T>C, and C>A, similar to common prostate cancer. The distribution of the variant allele frequency values indicated that these single cells are from the same tumor clone. The 69 single cells were clustered into tumor, stromal, and immune cells based on their global transcriptomic profiles. The tumor cells specifically express basal cell markers like KRT5, KRT14, and KRT23 and epithelial markers EPCAM, CDH1, and CD24. The transcription factor covariance network analysis showed that the BCC tumor cells have distinct regulatory networks. By comparison with current prostate cancer datasets, we found that some of the bulk samples exhibit basal cell signatures. Interestingly, at single-cell resolution the gene expression patterns of prostate BCC tumor cells show uniqueness compared with that of common prostate cancer-derived circulating tumor cells.
This study, for the first time, discloses the comprehensive mutational and transcriptomic landscapes of prostate BCC, which lays a foundation for the understanding of its tumorigenesis mechanism and provides new insights into prostate cancers in general.
作为前列腺癌的一种罕见亚型，基底细胞癌（BCC）尚未得到广泛研究，因此缺乏系统的分子特征描述。
在这里，我们应用单细胞基因组扩增和 RNA-Seq 技术对一例人前列腺 BCC（CK34βE12 / P63 / PAP / PSA）标本进行分析。通过对 49 个单细胞扩增混合物的全外显子测序获得了突变景观，并获得了 69 个单细胞的转录组。
BCC 中突变的五个假定驱动基因是 CASC5、NUTM1、PTPRC、KMT2C 和 TBX3，前三个核苷酸取代是 C>T、T>C 和 C>A，与常见的前列腺癌相似。变异等位基因频率值的分布表明这些单细胞来自同一个肿瘤克隆。根据其全局转录组谱，将 69 个单细胞聚类为肿瘤、基质和免疫细胞。肿瘤细胞特异性表达基底细胞标志物如 KRT5、KRT14 和 KRT23 以及上皮标志物 EPCAM、CDH1 和 CD24。转录因子协方差网络分析表明，BCC 肿瘤细胞具有独特的调控网络。与当前的前列腺癌数据集相比，我们发现一些批量样本表现出基底细胞特征。有趣的是，在单细胞分辨率下，与常见的前列腺癌衍生的循环肿瘤细胞相比，前列腺 BCC 肿瘤细胞的基因表达模式具有独特性。
本研究首次揭示了前列腺 BCC 的全面突变和转录组景观，为了解其肿瘤发生机制奠定了基础，并为一般的前列腺癌提供了新的见解。
